Interleukin-16 (IL-16; SEQ ID NO: 3) is a pro-inflammatory cytokine that induces positive chemotaxis of T-lymphocytes, monocytes, eosinophils, and dendritic cells (67 J. Leukocyte Biol. 757 (2000)). IL-16 stimulus also increases IL-1b expression, increases IL-6 expression, and increases IL-15 expression in IL-16 responsive eukaryotic cells (67 J. Leukocyte Biol. 757 (2000)).
IL-16 peptide chain monomers are formed by the caspase-3 mediated proteolytic processing of a larger 14 kDa precursor molecule (273 J. Biol. Chem. 1144 (1998)). IL-16 monomers form tetrameric peptide chain complexes. These tetrameric IL-16 complexes are believed to be the bioactive form of IL-16 (67 J. Leukocyte Biol. 757 (2000)). Eukaryotic cells that produce IL-16 include cells that express CD4 or CD8, such as T-cells, mast cells, eosinophils, dendritic cells epithelial cells, fibroblasts, and cells of the cerebellum (67 J. Leukocyte Biol. 757 (2000)). Eukaryotic cells responsive to IL-16 express the CD4 and CD9 peptide chains, but the response to IL-16 may also be independent of these peptide chains (see e.g. 164 J. Immunol. 4429 (2000)).
IL-16 has been reported to play an important role in such diseases as asthma, atopic dermatitis, and rheumatoid arthritis, among others (see e.g. 162 Am. J. Respir. Crit. Care Med. 105 (2000); 109 J. Allergy Clin. Immunol. 681 (2002); 31 J. Rheumatol. 35 (2004). For example, in human patients IL-16 has been shown to be responsible for attracting asthma inducing cells to the lungs and to play a critical role in triggering asthmatic responses in patients (162 Am. J. Respir. Crit. Care Med. 105 (2000)). Clearly, the ability to detect and identify molecules that activate or inhibit IL-16 is critical to the development of effective treatments for IL-16 mediate diseases.
Thus, a need exists for novel methods for detecting IL-16 biological activity, activators of IL-16 biological activity, and inhibitors of IL-16 biological activity.